title: Dual-targeted polyplexes: one step towards a synthetic virus for cancer gene therapy.
abstract: Incorporating ligands into nano-scale carriers for specific delivery of therapeutic nucleic acids to tumor sites is a promising approach in anti-cancer strategies. Current artificial vector systems however still suffer from efficient and specific delivery, compared to their natural counterparts and addressed receptor types rarely are exclusively expressed on target cells. In this study synthetic dual receptor targeted polyplexes were developed, mimicking biphasic cell entry characteristics of natural viruses to increase efficiency and specificity by a dual-receptor internalization mechanism. For engineering the synthetic dual targeted vector system, the transferrin targeting peptide B6 was evaluated for the first time in the context of PEGylated PEI based polyplexes. As a second ligand, arginine-glycine-aspartic acid (RGD) containing peptide was incorporated for simultaneous integrin targeting. Cellular association, cellular uptake, transfection efficiency and accordant competition experiments displayed specificity of both ligands for each targeted receptor in two prostate cancer cell lines. A clear synergy of dual targeting over the combination of single-targeted polyplexes was found, suggesting that the dual targeting strategy is one step towards safe vectors for therapeutic approaches.
authors.affiliation: Pharmaceutical Biotechnology, Center for Drug Research, and Center for NanoScience (CeNS), Ludwig-Maximilians-University, Butenandstr. 5-13, D-81377 Munich, Germany.
authors.forename: Yu
authors.initials: Y
authors.lastname: Nie
authors.forename: David
authors.initials: D
authors.lastname: Schaffert
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rödl
authors.forename: Manfred
authors.initials: M
authors.lastname: Ogris
authors.forename: Ernst
authors.initials: E
authors.lastname: Wagner
authors.forename: Michael
authors.initials: M
authors.lastname: Günther
mesh_terms: D045744:Cell Line, Tumor; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000235:genetics*; D008297:Male; D009369:Neoplasms / Q000235:genetics / Q000628:therapy*; D009842:Oligopeptides / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D011990:Receptors, Transferrin / Q000235:genetics*; D014162:Transfection
chemical_list: C000608267:B6 peptide; D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D011990:Receptors, Transferrin; D011092:Polyethylene Glycols; D011094:Polyethyleneimine